Related Experiment Video
Updated: Aug 22, 2025
Predictive Immune Modeling of Solid Tumors
Published on: February 25, 2020
Comparative assessment of early mortality risk upon immune checkpoint inhibitors alone or in combination with other
Giuseppe Viscardi1, Antonino C Tralongo2, Francesco Massari3
1Medical Oncology, Department of Precision Medicine, Università Degli Studi Della Campania "Luigi Vanvitelli", Naples, Italy; Department of Pneumology and Oncology, AORN Ospedali Dei Colli, Naples, Italy.
Background:
The early crossing of survival curves in randomised clinical trials (RCTs) with immune checkpoint blockers suggests an excess of mortality in the first months of treatment. However, the exact estimation of the early death (ED) rate, the comparison between ED upon immune checkpoint inhibitors (ICI) alone or in combination with other agents and the impact of tumour type, and PD-L1 expression on ED are unknown.
Methods:
RCTs comparing ICI alone (ICI-only group) or in combination with other non-ICI therapies (ICI-OT group) (experimental arms) versus non-ICI treatments (control arm) were included. ED was defined as death within the first 3 months of treatment. The primary outcome was the comparison of ED between experimental and control arms, and the secondary outcome was the comparison of ED risk between ICI-only and ICI-OT. ED rates estimated by risk ratio (RR) were pooled by random effect model.
Results:
A total of 56 RCTs (40,215 participants, 14 cancer types) were included. ED occurred in 14.2% and 6.7% of patients in ICI-only and ICI-OT groups, respectively. ED risk significantly increased with ICI-only (RR: 1.29, 95% CI 1.05-1.57) versus non-ICI therapies, while it was lower with ICI-OT versus non-ICI treatments (RR: 0.81, 95% CI 0.73-0.90). ED risk was significantly higher upon ICI-only compared to ICI-OT (RR: 1.57, 95% CI 1.26-1.95). Gastric and urothelial carcinoma were at higher risk of ED. PD-L1 expression and ICI drug classes were not associated with ED.
Conclusions:
ED upon first-line ICI is a clinically relevant phenomenon across solid malignancies, not predictable by PD-L1 expression but preventable through the addition of other treatments to ICI.
